Transferrin is an essential ingredient used in cell culture media due to its crucial role in regulating cellular iron uptake, transport, and utilization, and also a promising drug carrier to increase drug therapeutic index via its unique transferrin receptor-mediated endocytosis pathway. Transferrin currently in use is made mainly from blood plasma, and thus it carries a high risk of contamination with blood-borne pathogens while facing blood supply shortage. Recombinant production of transferrin protein is ideally situated to address both the safety concern and shortage problem of native transferrin for use in cell culture and drug delivery markets. Currently only limited quantity of yeast cell-expressed recombinant human transferrin is available at an extremely high price in the cell culture market. Ventria Bioscience already has produced the human lactoferrin, a close relative to human transferrin, in rice grains on large scale and at low lost. In this proposal, we plan to exploit similar technology used for large scale production of lactoferrin to express human transferrin in rice grains. The proposed studies will develop stable transgenic rice lines expressing recombinant human transferrin as a safe and low cost alternative to human blood derived transferrin for use in biopharmaceutical cell culture and drug delivery markets. Public Health Relevance: Transferrin plays a crucial role in regulating iron and is an essential ingredient used in cell culture medium and a potential candidate for drug conjugates. Transferrin used in cell culture is currently made from blood plasma, and thus carries a high risk of contamination with pathogens. Development of an affordable animal free source of recombinant human transferrin would enable safe large scale use of transferrin in cell culture and drug conjugates.